In the renewal application/Vulnerability Markers in Prodromal Schizophrenia," the first specific aim is to identify vulnerability markers for psychosis that are present in the prodromal phase and first episode of schizophrenia using 1) clinical, 2) neurophysiological, and 3) neurocognitive measures. Other aims are to increase our understanding of neurodevelopmental processes in individuals in the early stages of schizophrenia, to better understand pre-psychotic symptomatology and to determine the validity and efficiency of vulnerability markers in predicting evolution of psychosis and functional outcome. Increased knowledge regarding the onset of psychosis may help to better identify individuals who are at-risk for psychosis and provide insight into the neurodevelopmental processes that occur in this stage. Additional aims include assessment of at-risk individuals who do not make the transition to psychosis to better understand potential protective factors, decrease the rate of false positives, and decrease disability. Major hypotheses: 1) The at-risk and first episode groups will demonstrate abnormalities when compared to normals on measures of prepulse inhibition; visual masking; P50 gating; and neurocognition; 2) The trait- related deficits will be stable over time; and 3) The clinical and information processing measures will be differentially correlated with each other and one or more factors will predict psychotic conversion and functional outcome in the at-risk sample. The current proposal is unique in that it combines the current knowledge of clinical and demographic risk factors for schizophrenia with the rapidly emerging data on vulnerability markers, or endophenotypes, that are associated with schizophrenia. The use of brain-based vulnerability markers may help to identify neurobiologically and clinically meaningful subgroups within this heterogeneous population in the early stages of schizophrenia and determine which subjects would benefit from early treatment. Greater knowledge regarding protective factors and early indicators of functional outcome may also lead to targeted treatments in the early phase of the illness. Appropriate intervention at this early stage could possibly prevent or delay the development of a psychotic illness along with clinical and functional deterioration. The disruption of social networks, education and occupational activity and the high incidence of suicide and crime that often accompany psychosis might be reduced or averted. [unreadable] [unreadable] [unreadable]